Protein Involved in the Genetic Process may Combat Neurodegenerative Disorders

Deregulation of the cells that translate the genetic materials to reproduce, repair damage or even combat diseases may instead result in further damage. The damage to this precise cellular mechanism may contribute to errant processes where the byproducts accumulate around the neurons and cause neurodegenerative disorders such as Alzheimer’s disease.

A specific protein implicated in tumor growth may be able to help regulate awry cellular translation and protect against neuronal decay as per a study at the Hiroshima University, published in the journal Cell Reports.

“Researchers have begun to understand that age-related neurodegenerative diseases may be caused by slow but steady accumulation of toxic peptide products, which leads to death of neurons, such as beta-amyloid plaques causing Alzheimer’s disease. Repeat-associated non-AUG (RAN) translation is one of the mechanisms that generates such toxic products,” says lead paper author Katsura Asano, professor in Hiroshima University’s Graduate School of Integrated Sciences for Life and also in Division of Biology, Kansas State University.

The Translation Mechanism

Depending on the translation mechanism, the study team examined whether the translational regulatory protein 5MP can suppress RAN translation using electron microscopy and computer-directed modeling. This may in turn suppress the production of the toxic repeat peptide products.

It was found that 5MP competes with the protein it mimics in human cells and, when it wins, it reduces RAN translation and its toxic byproducts. The result was further validated in a model of engineered flies with fragile X-associated tremor ataxia syndrome (a neurodegenerative disorder).

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“Taken together, these data suggest that modulation of 5MP levels could be a viable therapeutic target by which to selectively reduce RAN translation in repeat expansion disorders. More studies on 5MP and the mechanism of translation can greatly contribute to the understanding and care of neurodegenerative diseases,” says Asano.

Source-Medindia